Beniamin Oskar Grabarek

miRNAs Participate in the Regulation of Oxidative Stress-Related Gene Expression in Endometrioid Endometrial Cancer

Reactive oxygen species are formed as by-products of normal cell metabolism. They are needed to maintain cell homeostasis and signaling, which is possible due to defense systems. Disruption of this balance leads to oxidative stress that can induce cancer. Redox regulation by miRNAs may be a potential therapeutic target. The aim of the study was to assess the activity of genes associated with oxidative stress in endometrial cancer and to determine their relationship with miRNAs. The study included 45 patients with endometrioid endometrial cancer and 45 without neoplastic changes. The expression profile of genes associated with oxidative stress was determined with mRNA microarrays, RT-qPCR and ELISA. The miRNA prediction was performed based on the miRNA microarray experiment and the mirDB tool. PRDX2 and AQP1 showed overexpression that was probably not related to miRNA activity. A high level of PKD2 may be the result of a decrease in the activity of miR-195-3p, miR-20a, miR-134. A SOD3 level reduction can be caused by miR-328, miR-363. In addition, miR-363 can also regulate KLF2 expression. In the course of endometrial cancer, the phenomenon of oxidative stress is observed, the regulation of which may be influenced by miRNAs.

Recent Multiomics Approaches in Endometrial Cancer

Endometrial cancer is the most common gynecological cancers in developed countries. Many of the mechanisms involved in its initiation and progression remain unclear. Analysis providing comprehensive data on the genome, transcriptome, proteome, and epigenome could help in selecting molecular markers and targets in endometrial cancer. Multiomics approaches can reveal disturbances in multiple biological systems, giving a broader picture of the problem. However, they provide a large amount of data that require processing and further integration prior to analysis. There are several repositories of multiomics datasets, including endometrial cancer data, as well as portals allowing multiomics data analysis and visualization, including Oncomine, UALCAN, LinkedOmics, and miRDB. Multiomics approaches have also been applied in endometrial cancer research in order to identify novel molecular markers and therapeutic targets. This review describes in detail the latest findings on multiomics approaches in endometrial cancer.

Evaluation of the Impact of Cisplatin on Variances in the Expression Pattern of Leptin-Related Genes in Endometrial Cancer Cells

This research aimed to assess the impact of cisplatin, depending on the concentration and exposure time, on the expression pattern of leptin in an endometrial cancer cell line. Ishikawa endometrial cancer cell cultures were incubated with cisplatin, at concentrations of 2.5–10 µM, or leptin in the concentration range 10–40 ng/mL, and for durations of 12, 24 and 48 h compared with the control. The microarray techniques: RTqPCR; ELISA; and RNAi assay were used. Statistical analysis was performed at p < 0.05. Already with the lowest concentration and incubation time, statistically substantial silencing of leptin expression on the mRNA level under the influence of cisplatin after its addition to the culture was observed. On the protein level, the expression for cisplatin at a concentration of 2.5 µM was only noticeable after 48 h of exposure and maintained themselves with consecutively larger concentrations. It was observed that cisplatin at a concentration of 5 µM is IC50 and the drug activated apoptosis via caspases -3 and -9. Cisplatin at a concentration of 5 µM and higher has a significant effect on the concentration of leptin. The effect of cisplatin on the expression profile of genes associated with leptin-dependent signaling pathways and changes in the expression of leptin itself and its receptors was confirmed. It was also confirmed that cisplatin exerted its effect via the leptin pathway.